Cardiovascular Disease In Offspring Research Articles

High-Fat Diet, Epigenetics, and Atherosclerosis: A Narrative Review.

Atherosclerosis is a chronic inflammatory disease developing and progressing in the presence of risk factors including hyperlipidemia, hypercholesterolemia, and chronic inflammation, among others. Atherosclerosis commonly precipitates as ischemic events, transient ischemic attacks, and myocardial infarction. Saturated fatty acids are risk factors; however, their association with epigenetics in the pathophysiology of atherosclerosis is not clearly understood. The preclinical and clinical trials associating atherosclerosis with epigenetics are scarcely documented, and most of the studies reported the use of drugs inhibiting methylation and histone modification to improve atherosclerosis. This narrative review aims to discuss various aspects and the association between a high-fat diet, epigenetic reprogramming, and atherosclerosis. A literature search with the keywords high-fat diet, epigenetics, and atherosclerosis, alone or in combination, was conducted to search for articles in the English language. Duplicate articles were removed, and articles related to the subject of this review article were included in this review. A review of the literature suggests that a high-fat diet with saturated fatty acids is a risk factor for atherosclerosis, but this association is multifactorial, and epigenetics play a critical role. However, the connecting link and the underlying molecular and cellular mechanisms are not clearly understood yet and warrant more research. A high-fat diet rich in saturated fatty acids is a risk factor for atherosclerosis involving epigenetic reprogramming and altered gene expression. The existing preclinical and clinical trials support the role of epigenetics and reversing it using drugs to attenuate atherosclerosis, but definitive evidence warrants larger clinical trials. Further, a high-fat diet in pregnant mothers can manifest as cardiovascular disease in offspring; caution must be taken in pregnant mothers for their diet and nutrients.

Placental Pathology and Blood Pressure at Age 7: A Longitudinal Discordant Twin Analysis.

Evidence suggests that the intrauterine environment shapes offspring cardiovascular disease risk. Although placental dysfunction may be an important pathophysiologic pathway, numerous parental and pregnancy characteristics that influence offspring blood pressure are strong confounders of the mechanistic role of the placenta in observational analyses of singletons. Therefore, we leverage twin- and sibling-based comparison designs to determine whether placental pathology is associated with offspring blood pressure at age 7 while mitigating major sources of confounding. Data are from pregnant participants and their offspring in the Collaborative Perinatal Project, a longitudinal pregnancy cohort conducted from 1959 to 1965 in the United States. After delivery, placentas were systematically examined for lesions indicative of maternal vascular malperfusion (MVM) and acute inflammation. Blood pressure was assessed at a follow-up research visit when the offspring were 7 years old. Linear fixed-effects models were used to estimate associations between within-twin or sibling discordance in placental pathology and differences in blood pressure at age 7. Overall, 193 twin pairs were eligible for inclusion, and 23.3% had placentas discordant for MVM. In a fixed-effect analysis, a twin with high-grade MVM had a higher systolic blood pressure Z score by 0.56 SDs than their co-twin without MVM (95% CI, 0.06-1.05) or a 5.7-mm Hg difference (95% CI, 0.6-10.8). Associations were consistent in a sensitivity analysis restricted to dichorionic twins and in a secondary analysis of 759 MVM-discordant sibling pairs. Acute placental inflammation was not associated with blood pressure at age 7. MVM in the placenta is associated with higher offspring blood pressure in mid-childhood, independent of parental and pregnancy characteristics that twins have in common. The findings support the role of the placenta and the intrauterine environment in the developmental origins of cardiovascular health.

Maternal polycystic ovary syndrome and Offspring’s Risk of Cardiovascular diseases in Childhood and Young Adulthood

Children born to mothers with polycystic ovary syndrome have a higher prevalence of cardiovascular risk factors and of subclinical cardiovascular disease, but the association between maternal polycystic ovary syndrome and cardiovascular disease in offspring is unclear. We conduct a register-based cohort study of 6 839 703 live singleton births from Denmark (1973–2016) and Sweden (1973–2014) and follow them for up to 48 years. Using Cox regression models, we find that offspring of mothers with polycystic ovary syndrome have a higher risk of overall cardiovascular diseases and of its specific subtypes, independently of comorbidities related to polycystic ovary syndrome. Cousin analyzes suggest that familial confounding does not explain our results. If our findings are replicated by future studies, children of women with polycystic ovary syndrome may benefit from early cardiovascular prevention efforts.

Epigenetic mechanisms linking pregnancy complications to cardiovascular disease in offspring

Epigenetic mechanisms linking pregnancy complications to cardiovascular disease in offspring

Maternal exposure to polystyrene nanoplastics induces sex-specific cardiotoxicity in offspring mice

Globally, plastic pollution threatens human health, particularly affecting the hearts of offspring exposed to maternal environmental factors early in development. Few studies have specifically addressed sex-specific cardiac injury in offspring resulting from maternal exposure to polystyrene nanoplastics (PS-NPs). This study investigates the potential cardiac injury in offspring following maternal exposure to 1 mg/L PS-NPs. Pregnant C57BL/6J mice were exposed to PS-NPs until 3 weeks postpartum to establish a maternal exposure model. Heart tissues were collected and weighed, and the transcriptomes of the offspring hearts were sequenced and analyzed using high-throughput RNA sequencing. Immunohistochemical staining was performed to assess the effects of PS-NPs on cardiac immune infiltration, fibrosis, and apoptosis in the offspring. PS-NPs caused a significant reduction in heart and body weight in female offspring compared to males. Additionally, PS-NPs induced sex-specific transcriptional reprogramming and metabolic disruptions in the offspring. PS-NPs also induced significant fibrosis, apoptosis, and increased CD68+ macrophage infiltration in offspring hearts. Notably, PS-NPs induced distinct cardiovascular diseases in the offspring. Fluid shear stress and atherosclerosis were significantly enriched in PS-NP-treated male offspring, while viral myocarditis was predominantly enriched in PS-NP-treated females. Our findings suggest that PS-NPs induce cardiotoxicity in offspring by disrupting metabolism, impairing immunity, and triggering fibrosis and apoptosis, with sex-specific differences. This study provides novel insights and a foundation for understanding sex-specific pharmacological differences and interventions in PS-NP-induced cardiovascular disease in offspring.

Pre-existing maternal cardiovascular disease and the risk of offspring cardiovascular disease from infancy to early adulthood.

A variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control. This nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding. Of the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02). Maternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Maternal exercise preserves offspring cardiovascular health via oxidative regulation of the ryanodine receptor

ObjectiveThe intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated. MethodsTo determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 52 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies. ResultsHigh-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 52 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring. ConclusionsThese data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.

Maternal Hypercholesterolemia is a Significant Risk Factor for Atherogenesis – A Systematic Review

Background: Cardiovascular diseases, typically associated with older individuals, have been found to have risk factors that can develop during childhood and even fetal development. Maternal hypercholesterolemia, experienced during pregnancy, is one such factor that affects the fetus. This review aims to explore the mechanisms through which maternal hypercholesterolemia can contribute to the development of atherosclerosis and subsequent cardiovascular diseases and events. Methods: To conduct this review, we systematically analyzed existing literature and collected relevant information on the impact of maternal hypercholesterolemia on fetal development and subsequent cardiovascular health. We examined studies that investigated the pathways and mechanisms by which maternal hypercholesterolemia influences atherosclerosis and its related diseases. Results: Our review identified several mechanisms by which maternal hypercholesterolemia can stimulate the development of atherosclerosis and contribute to cardiovascular diseases and events. These mechanisms include alterations in lipid metabolism, oxidative stress, endothelial dysfunction, inflammation, and vascular remodeling. Maternal hypercholesterolemia during pregnancy can lead to lipid abnormalities in the fetus, triggering early atherosclerotic changes that persist into adulthood. These changes may increase the risk of cardiovascular diseases later in life. Conclusion: This review highlights the potential impact of maternal hypercholesterolemia on the development of atherosclerosis and subsequent cardiovascular diseases in offspring. Understanding the mechanisms involved is crucial for developing effective preventive strategies and interventions. By addressing maternal hypercholesterolemia and its effects during pregnancy, healthcare providers can contribute to reducing the burden of cardiovascular diseases in future generations. Further research is needed to elucidate the precise mechanisms and long-term effects, which will aid in developing targeted approaches for early intervention and risk mitigation.

Cardiovascular health of offspring conceived by assisted reproduction technology: a comprehensive review.

Recently, the use of assisted reproductive technology (ART) has rapidly increased. As a result, an increasing number of people are concerned about the safety of offspring produced through ART. Moreover, emerging evidence suggests an increased risk of cardiovascular disease (CVD) in offspring conceived using ART. In this review, we discuss the epigenetic mechanisms involved in altered DNA methylation, histone modification, and microRNA expression, as well as imprinting disorders. We also summarize studies on cardiovascular changes and other risk factors for cardiovascular disease, such as adverse intrauterine environments, perinatal complications, and altered metabolism following assisted reproductive technology (ART). Finally, we emphasize the epigenetic mechanisms underlying the increased risk of CVD in offspring conceived through ART, which could contribute to the early diagnosis and prevention of CVD in the ART population.

Preeclampsia's Cardiovascular Aftermath: A Comprehensive Review of Consequences for Mother and Offspring.

Preeclampsia (PE), a multisystem hypertensive disorder affecting 2-8% of pregnancies, has emerged as a novel risk factor for cardiovascular disease (CVD) in affected mothers and in their offspring. Between 10 and 15 years following gestation, women with a history of PE have double the risk of CVD, nearly 4 times the risk of hypertension, and increased all-cause mortality. Offspring exposed to PE in utero carry an increased risk of CVD and congenital heart defects. Due to the multifactorial nature of both PE and CVD, a clear dependency has been difficult to establish. The interplay between CVD and PE is an area of active investigation, likely involving placental, genetic, and epigenetic factors resulting in enduring endothelial, vascular, and immune dysfunction. Fetal developmental programming induced by adverse intrauterine environments, epigenetic changes triggered by oxidative stress, and underlying genetic predisposition play pivotal roles in the development of CVD in offspring exposed to PE. Though the literature has discussed the cardiovascular outcomes associated with PE for nearly a decade, patient risk perception and health care provider awareness remain low, representing a substantial missed opportunity for early intervention in this vulnerable population. This review article will discuss the pathophysiology of preeclampsia, its intersection with CVD, and the long-term cardiovascular consequences for affected mothers and their offspring. Our objective is to increase health care provider awareness and garner greater research interest in this important topic.

The risk of pediatric cardiovascular diseases in offspring born to mothers with systemic lupus erythematosus: a nationwide study.

Systemic lupus erythematosus (SLE), a common autoimmune disease predominantly affecting women, has been linked to various complications during pregnancy. The transfer of anti-Ro/SSA antibodies from SLE-affected mothers to their offspring can lead to neonatal lupus and cardiac issues. This study investigated the association between maternal SLE and the risk of pediatric cardiovascular disorders. The study utilized South Korea's National Health Insurance Service (NHIS) database, covering 3,505,737 children born between 2007 and 2017 and tracked until 2020. Maternal SLE cases were identified using the World Health Organization's International Classification of Diseases Tenth revision (ICD-10) codes and linked with delivery records. Cardiologic disorders were categorized into congenital heart disease (CHD), arrhythmic disorders, and acquired heart disease. Propensity score matching with 1:4 ratios was applied to the set control group. Among 3,505,737 children, 0.7% (n = 23,330) were born to mothers with SLE. The incidence of preterm birth was significantly higher in the maternal SLE group (5.9% vs. 3.0%). Compared with the control group, children born to mothers with SLE exhibited a significantly elevated risk of overall CHDs (5.5%, adjusted odds ratio [aOR] 1.21; 95% confidence interval [CI] 1.14-1.29), including atrial septal defect (1.18; 1.09-1.28) and patent ductus arteriosus (1.15; 1.03-1.30). In addition, a notably higher risk was observed in arrhythmic disorders (complete atrioventricular block 7.20; 2.41-21.49) and acquired cardiac disorders, including cardiomyopathy (1.40; 1.17-1.68) and mucocutaneous lymph node syndrome (MCLS) (1.27; 1.15-1.43). Maternal SLE is associated with congenital and acquired cardiac disorders in offspring, including structural, arrhythmic, and MCLS. This study highlights the need for continuous cardiovascular monitoring from the prenatal stage to preadolescence in these children due to multifactorial influences involving maternal autoantibodies, genetic predisposition, and environmental factors.

Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells via PCDH10 in Gestational Diabetes Mellitus.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms through which these complications occur are due to functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), which remain less defined. We confirm that intrauterine hyperglycemia leads to the impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with the hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in the offspring of GDM mothers.

Abstract 13282: Parental Allostatic Load Predicts Time to the Onset of Cardiovascular Disease in Offspring

Background: Allostatic load, a measure of cumulative stress-related physiologic dysregulation, is associated with major cardiovascular disease (CVD) events. However, despite evidence of familial aggregation of CVD risk factors, the impact of parental allostatic load on the onset and timing of CVD in offspring remains unknown. Hypothesis: We hypothesize that offspring of parents with lower allostatic load will have longer CVD-free survival time. Aim: To examine whether CVD-free survival in offspring is associated with parental allostatic load and potential sex-specific differences. Methods: A secondary data analysis of 6,145 offspring-mother-father trios derived from the Framingham Heart Study Original (exam 10) and Offspring Cohorts (exam 1). Allostatic load was defined as an index (0-16) of 8 variables (systolic and diastolic blood pressure, total cholesterol, HDL, LDL, total cholesterol/ HDL ratio, fasting blood glucose and body mass index). Kaplan-Meier plots, and Irwin’s restricted mean and multivariable-adjusted Cox proportional hazards regression models were used to examine sex-specific differences and the association between parental allostatic load and offspring’s CVD-free survival. Results: Parents mean age (SD) was 60.8 (8.1) and offspring’s 34.8 (10.5). 22.8% of parents (n=458) and 12.1% (n=412) of offspring had high allostatic load (>8). In a total of 118,132 person-years of follow-up among the offspring, 1060 incident CVD events occurred. The overall CVD incidence rate was 8.9 per 1000 person-years (95% confidence interval [CI] 8.4-9.5) and sons had a higher CVD incident rate than daughters (11.0 vs 7.2, p<0.001). Offspring of mothers with low allostatic load lived 4 more years free of CVD compared to offspring of mothers with high allostatic load. Similarly, offspring of fathers with low allostatic load lived 3 more years free of CVD. The hazard rate of having incident CVD among offspring of mothers and fathers with high (compared to low) allostatic load was 1.58 (1.28-1.95) and 1.39 (95% CI: 1.11-1.75), respectively. Conclusion: Parents' allostatic load has a significant impact on the cardiovascular health of their offspring, with those of mothers with high allostatic load being at a higher risk of developing CVD at a younger age.

Family History of Modifiable Risk Factors and Association With Future Cardiovascular Disease.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent-child trios in the multigenerational longitudinal Framingham Heart Study. We assessed parental history of CVD and modifiable risk factors (smoking, hypertension, diabetes, obesity, and hyperlipidemia). Multivariable Cox models were used to evaluate the association of parental history and future CVD among offspring. Among 6278 individuals (mean age 45±11 years), 44% had at least 1 parent with history of CVD. Over a median follow-up of 15 years, 353 major CVD events occurred among offspring. Parental history of CVD conferred 1.7-fold increased hazard of future CVD (hazard ratio[HR], 1.71 [95% CI, 1.33-2.21]). Parental obesity and smoking status were associated with higher hazard of future CVD (obesity: HR, 1.32 [95% CI, 1.06-1.64]; smoking: HR, 1.34 [95% CI, 1.07-1.68], attenuated after adjusting for offspring smoking status). By contrast, parental history of hypertension, diabetes, and hypercholesterolemia were not associated with future CVD in offspring (P>0.05 for all). Furthermore, parental risk factors did not modify the association of parental CVD history on future offspring CVD risk. Conclusions Parental history of obesity and smoking were associated with a higher hazard of future CVD in offspring. By contrast, other parental modifiable risk factors did not alter offspring CVD risk. In addition to parental CVD, the presence of parental obesity should prompt a focus on disease prevention.

Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control.

Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. The rat model of IUH was established by exposure to 10% O2 seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg-1.d-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

Abstract 18: Impact of Preeclampsia on Cardiovascular Risk Factors in Mothers and Newborns

Introduction: Preeclampsia is a multifactorial disease and a cause of maternal and neonatal morbidity and mortality. Women with preeclampsia have increased risk of cardiovascular diseases in later life. The impact on the offspring is, however, still uncertain. Lipid traits in newborns are considered to reflect the child’s own production. Hypothesis: We assessed the hypothesis that preeclampsia increases risk of future cardiovascular disease in both mother and offspring. Methods: For this purpose, we used the Copenhagen General Population Study comprising 59,571 women of which 1,365 had a diagnosis of preeclampsia to investigate the association between preeclampsia and risk of cardiovascular diseases. Further, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and assessed the impact of preeclampsia on atherogenic lipid traits in cord blood. Results: Age adjusted hazard ratios for preeclampsia versus no preeclampsia (95% CI) were 1.48 (1.13-1.94) for ischemic heart disease, 1.50 (1.07-2.12) for ischemic cerebrovascular disease, and 1.53 (1.22-1.91) for composite vascular disease. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.31 (1.00-1.72), 1.44 (1.02-2.02), and 1.39 (1.11-1.74). Concentrations of non-HDL cholesterol, total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in cord blood increased stepwise from no preeclampsia (n=11,221) to mild/moderate preeclampsia (n=253) to severe preeclampsia (n=104) (p for trends <0.0001 for non-HDL cholesterol, total cholesterol and LDL cholesterol; p for trend=0.0002 for apolipoprotein B; p for trend=0.003 for triglycerides). Multivariable adjusted odds ratios (95% CI) for preeclampsia versus no preeclampsia (reference) for cord blood concentrations above the 80 th percentile were 2.09 (1.67-2.61) for non-HDL cholesterol, 1.58 (1.25-2.01) for total cholesterol, 1.72 (1.37-2.16) for LDL cholesterol, 1.38 (1.07-1.78) for apolipoprotein B, and 2.64 (2.07-3.35) for triglycerides. Conclusion: Women with preeclampsia had increased risk of future cardiovascular disease and lipid traits in umbilical cord blood of their offspring were elevated. This indicates that preeclampsia affects lipid metabolism during fetal life and potentially contributes to an increased risk of future cardiovascular disease in offspring of mothers with preeclampsia.

Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood: a nationwide population-based cohort study

BackgroundMaternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.MethodsUsing Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring’s age as the time scale.ResultsDuring a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20–1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38–1.78) and gestational diabetes (HR=1.37, 95% CI=1.25–1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98–1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00–1.88) or preeclampsia (HR=1.62, 95% CI=1.41–1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42–2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17–1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06–2.41), 1.29 (1.04–1.59), and 1.38 (1.24–1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85–5.60) than offspring of mothers with HDP or diabetes alone.ConclusionsOffspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

Histological Studies of the Heart and Biochemical Changes Due to the Perinatal Consumption of Hibiscus sabdariffa (Flavonoid-rich Extract) to Feed-restricted Rats on Offspring

Background: Experiments using animal models have indicated that maternal diet during the perinatal period can drastically impact the life-long susceptibility of offspring to chronic disease. Objectives: This study aims to determine the impact of perinatal consumption of Hibiscus sabdariffa to feed restriction on offspring heart development. Methods: In this study, we used 25 pregnant rats. They were grouped as follows: group 1 (normal control), group 2 (70% feed restriction), group 3 (70% feed restriction and 5mg/kg body weight of H. sabdariffa administration), group 4 (70% feed restriction, and 10mg/kg body weight of H. sabdariffa administration), and group 5 (70% feed restriction and 20mg/kg body weight of H. sabdariffa administration). Dams were only allowed to nurse 8 pups. Pups were weaned and observed daily for puberty onset. Blood samples were collected to determine serum levels of creatine kinase, hydrogen peroxide, and malondialdehyde. The hearts were excised, weighed, and prepared for histological examination. Results: The result showed a significant increase in absolute and relative weights of the heart with alterations in the histology of the heart. There was a significant change in serum levels of creatine kinase and malondialdehyde. Conclusion: Maternal consumption of H. sabdariffa during pregnancy and lactation may increase the development of cardiovascular diseases in offspring during postnatal growth.

Association of Parental Cardiovascular Health With Disability-Adjusted Life Years in the Offspring: Results From the Framingham Heart Study.

Disability-adjusted life years (DALYs) are used to evaluate the relative burden of diseases in populations to help set prevention or treatment priorities. The impact of parental cardiovascular health (CVH) on healthy life years lost from cardiovascular disease (CVD) in adult offspring is unknown. We compared parent-offspring CVD DALYs trends over the life course and examined the association of parental CVH with offspring CVD DALYs. Using data from the Framingham Heart Study, 4814 offspring-mother-father trios were matched for age at selected baseline exams. CVH score was computed from the number of CVH metrics attained at recommended levels: poor (0-2), intermediate (3-4), and ideal (5-7). CVD DALYs were defined as the sum of years of life lost and years lived with CVD. Age-sex-standardized life expectancy and disability weights were derived from the actuarial life tables and Global Burden of Disease study, respectively. Multivariable-adjusted linear regression was used to investigate the association of parental CVH with offspring CVD DALYs. Over an equal 47-year follow-up, parents lost nearly twice the number of CVD DALYs compared to their offspring (23 234 versus 12 217). However, age-adjusted CVD DALYs were higher at younger ages and similar along the life course for parents and offspring. One-unit increase in parental CVH was associated with 5 healthy life months saved in offspring. Offspring of mothers with ideal versus poor CVH had 3 healthy life years saved (β=-3.0 DALYs [95% CI, -5.6 to -0.3]). No statistically significant association was found between paternal CVH categories and offspring CVD DALYs. Higher maternal and paternal CVH were associated with increased healthy life years in offspring; however, the association was strongest between mothers and offspring. Investment in CVH promotion along the life course has the potential to reduce the burden of CVD in the current and future generation of adults.